The goal of this small business innovation research grant is to develop and commercialize a highly accurate, minimally invasive risk stratification technique for colorectal cancer (CRC) that is simple enough to be performed by the primary care provider during an annual physical exam. Although existing guidelines recommend CRC screening for all patients over age 50 (>100 million Americans), CRC remains the second leading cause of cancer death. This is in part due to the limitations in the existing CRC screening techniques including colonoscopy which is considered a 'gold standard' for CRC screening. This is because only a small fraction of eligible population undergoes colonoscopy due to variety of reasons including expense, patient reluctance, complications, and insufficient number of endoscopists. Furthermore, the current practice of colonoscopy on the average risk population is remarkably inefficient as only ~6% of the screening population have significant neoplasia (advanced adenomas). Hence developing a minimally invasive test to identify patients who do and do not harbor colonic adenomas is of crucial importance to better target patients for colonoscopy. This would enable, for the first time, a population wide screening for CRC. An interdisciplinary team of engineers, biologists and clinicians at Northwestern University and Northshore University HealthSystem has developed Partial Wave Spectroscopic (PWS) Microscopy, a novel biophotonic technique that enables sensing the nanoscale intracellular architectural correlates of the genetic/epigenetic changes in otherwise cytopathologically normal mucosa cells. Preliminary animal and human studies demonstrated the potential of PWS microscopy to detect subtle alterations in cytologically normal-appearing cells that are due to the presence of cancerous/precancerous lesions present in a different part of an organ, a consequence of the well-established concept of field carcinogenesis. This opens a possibility to detect the presence of colonic neoplasia by means of PWS analysis of cells from rectal mucosa, which is readily accessible by a simple brushing of the cells without the need for colonoscopy or bowel preparation. Indeed, in pilot studies on 146 patients it was noted that the PWS marker from endoscopically-normal rectal mucosal brushings mirrored the significance of neoplastic lesions elsewhere in the colon (advanced adenomas > adenomas > no neoplasia). There are several steps that are required prior to the future definitive clinical validation of rectal PWS analysis. In phase I of this SBIR, an automated PWS microscopy with high throughput capability will be developed and tested for its nanoscale sensitivity and diagnostic potential. In phase II, a standard operating procedure will be developed that will optimize the sample collection, sample processing and PWS analysis algorithms. The automated PWS system and the SOP will be tested on 300 patients (training set, n = 200 and validation set, n = 100). The successful SBIR research would enable NanoCytomics to create a commercially viable diagnostic system that would be critical for future multi-center clinical trials and FDA approval. PUBLIC HEALTH RELEVANCE: Existing colorectal cancer screening techniques do not allow accurate and cost-effective screening of the entire at-risk population - all patients over 50 years age (> 100 million Americans). This SBIR project will lead towards the development of a highly sensitive, minimally invasive and commercially viable optical technology that would enable screening general population by a simple brushing of rectum that can be performed by the primary care physician at an annual physical exam.